RAT ANTIGEN-INDUCED ARTHRITIS - CARTILAGE ALTERATIONS ASSESSED WITH IODINE-123-ANTILEUKOPROTEINASE

Imaging of cartilage alterations was attempted in joints of rats with chronic antigen-induced arthritis (AIA) using the cationic I-123-label ed serine proteinase inhibitor antileukoproteinase (I-123-ALP; pl > 10 ), which selectively accumulates in normal cartilage, presumably throu gh interaction with negatively charged proteoglycans. Methods: Iodine- 123-ALP or I-123-myoglobin, a control protein of comparable size but w ith different isoelectric point (pl = 7.3) was injected intravenously into normal or AIA rats. Joint accumulation was followed by scintigrap hy for 14 hr. Tissue radioactivity was assessed by well-counter measur ements after dissection. The content of charged molecules in articular cartilage was determined by toluidine blue staining; the degree of jo int destruction was assessed in parallel by x-ray, ex vivo MRI and his topathology. Results: In intact articular cartilage, ALP accumulated t o a significantly higher degree than myoglobin. This preferential accu mulation was lost in rats with chronic AIA. The target-to-background r atio for I-123-ALP negatively correlated with the loss of toluidine bl ue staining in cartilage, which documents depletion of charged matrix molecules (r = -0.92, p < 0.01 at 4 hr; r = -0.97, p < 0.01 at 13 hr). ALP scintigraphy was sensitive in detecting cartilage alterations, ev en though the degree of joint destruction and inflammatory infiltratio n was mild, as demonstrated by x-ray, MRI and histopathology, Conclusi on: In rat AIA, loss of ALP accumulation appears to document proteogly can depletion in mildly altered arthritic cartilage. ALP scintigraphy may represent a functional assay for early, premorphological cartilage alterations in human arthritis as well.